pilot study of budesonide for patients with primary sclerosing cholangitis

Conditions: Cholangitis, Sclerosing; Liver Cirrhosis, Biliary

Summary: objectives: i. assess the safety and effectiveness of budesonide in patients with primary sclerosing cholangitis or primary biliary cirrhosis experiencing a suboptimal response to ursodeoxycholic acid. ii. estimate the efficacy of this therapy in these patient groups as a means of evaluating the feasibility of a long-term randomized trial.

protocol outline: patients receive budesonide by mouth 3 times daily for a minimum of 6 months. if liver biochemistries become normal, dosage is reduced to once daily. treatment discontinues after 1 year.

Eligibility criteria:
protocol entry criteria: --disease characteristics-- pathologically confirmed primary sclerosing cholangitis (psc) meeting the following criteria: * chronic cholestatic disease for at least 6 months * liver biopsy within the past 6 months compatible with the diagnosis of psc intra and/or extrahepatic biliary duct obstruction, beading, or narrowing or pathologically confirmed primary biliary cirrhosis (pbc) that is experiencing suboptimal response to ursodeoxycholic acid and meeting the following criteria: * chronic cholestatic liver disease for at least 6 months * positive antimitochondrial antibody * no biliary obstruction by ultrasound, ct, or cholangiography * prior liver biopsy compatible with diagnosis of pbc * received ursodeoxycholic acid for at least 6 months --prior/concurrent therapy-- biologic therapy: * at least 3 months since prior d-penicillamine * no planned transplantation for at least 1 year chemotherapy: * at least 3 months (6 months for pbc) since prior cyclosporin, colchicine, azathioprine, or methotrexate * at least 6 months since prior chlorambucil (pbc only) endocrine therapy: at least 3 months (6 months for pbc) since prior corticosteroids surgery: no prior intraductal stones or operations on the biliary tree except cholecystectomy (psc only) other: * at least 3 months since prior pentoxifylline, ursodeoxycholic acid, or nicotine (psc only) * at least 6 months since prior chenodeoxycholic acid (pbc only) --patient characteristics-- life expectancy: at least 3 years hematopoietic: not specified hepatic: * alkaline phosphatase at least 2 times upper limits of normal * no chronic hepatitis b infection * no hepatitis c infection * no autoimmune hepatitis * bilirubin no greater than 4 mg/dl (pbc only) cardiovascular: no severe cardiopulmonary disease other: * no concurrent advanced malignancy * at least 3 months since prior inflammatory bowel disease requiring specific treatment except maintenance therapy (psc only) * no anticipated need for transplantation within 1 year * not pregnant * no liver disease of other etiology such as: chronic alcoholic liver disease hemochromatosis wilson's disease congenital biliary disease cholangiocarcinoma no recurrent ascending cholangitis requiring hospitalization more than 2 times per year (psc only) at least 1 year since prior active peptic ulcer no recurrent variceal bleeds no spontaneous encephalopathy no diuretic-resistant ascites

Keywords: cirrhosis gastrointestinal disorders primary biliary cirrhosis primary sclerosing cholangitis rare disease